N-Methylaniline → HCID 178482821, compound

HRID 736278Notes

Reaction equation

[CH3:1][NH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[CH2:10][C:11]1[CH:45]=[CH:44][C:14]([C:15]([NH:17][C:18]2[C:19]3[CH:32]=[C:31]([C:33]([NH:35][N:36]([CH3:43])[C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)=[O:34])[S:30][C:20]=3[N:21](C(OC(C)(C)C)=O)[N:22]=2)=[O:16])=[CH:13][CH:12]=1.ClCC1C=CC(C(NC2C3C=C(C(NN(C4C=CC(Cl)=CC=4)C)=O)SC=3N(C(OC(C)(C)C)=O)N=2)=O)=CC=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[CH3:1][N:2]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([C:15]([NH:17][C:18]2[C:19]3[CH:32]=[C:31]([C:33]([NH:35][N:36]([CH3:43])[C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)=[O:34])[S:30][C:20]=3[NH:21][N:22]=2)=[O:16])=[CH:44][CH:45]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 25 °C

Procedure

27 mg (74 μmol) of tetrabutylammonium iodide and 121 μL (1.11 mmol) of N-methylaniline are successively added to a solution of 200 mg (0.37 mmol) of an approximately 70:30 mixture of tert-butyl 3-(4-chloromethylbenzoylamino)-5-(N′-methyl-N′-phenylhydrazinocarbonyl)thieno[2,3-c]pyrazole-1-carboxylate and tert-butyl 3-(4-chloromethylbenzoylamino)-5-(N′-(4-chlorophenyl)-N′-methylhydrazinocarbonyl)thieno[2,3-c]pyrazole-1-carboxylate in 6 mL of dimethylformamide under argon. The reaction mixture is stirred at a temperature in the region of 25° C. for 15 days, and then poured onto ice. It is then extracted twice with a 50/50 mixture of ethyl acetate and heptane. The organic extracts are combined, washed with saturated brine, dried over magnesium sulfate and then concentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C. The residue is dissolved in 4 mL of methanol and the solution is introduced into a microwave oven tube. The tube is stoppered and the reaction mixture is irradiated at a temperature in the region of 100° C. for 30 minutes. The reaction mixture is then concentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C. The residue is purified by chromatography on a cartridge of 15 g of silica gel (0.015-0.040 mm), eluting with pure dichloromethane and then with a dichloromethane/methanol/28% aqueous ammonia mixture (12/3/0.5 by volume) at a flow rate of 10 mL/min. The fractions containing the expected product are combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is purified by preparative LC/MS (conditions B). 11 mg of 4-[(methylphenylamino)methyl]-N-[5-(N′-methyl-N′-phenylhydrazinocarbonyl)-1H-thieno[2,3-c]pyrazol-3-yl]benzamide are thus obtained in the form of a beige-colored powder melting at 242° C. LC-MS-DAD-ELSD: 511(+)=(M+H)(+).

Workup

additionpoured onto ice
extractionIt is then extracted twice with a 50/50 mixture of ethyl acetate and heptane
washwashed with saturated brine
dry with materialdried over magnesium sulfate
concentrationconcentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C
dissolutionThe residue is dissolved in 4 mL of methanol
additionthe solution is introduced into a microwave oven tube
customthe reaction mixture is irradiated at a temperature in the region of 100° C. for 30 minutes
concentrationThe reaction mixture is then concentrated to dryness under vacuum (2 kPa) at a temperature in the region of 40° C
customThe residue is purified by chromatography on a cartridge of 15 g of silica gel (0.015-0.040 mm)
washeluting with pure dichloromethane
additionThe fractions containing the expected product
concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
customThe residue is purified by preparative LC/MS (conditions B)

Sources & evidence

ORD record: ord-c9bd751b24584e6590ccf93a6042ef7a
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07595320B2

Reaction notes

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